Impact of down-regulation of histone methyltransferase enhancer of zeste homolog 2 on RUNX3 expressions, proliferation and apoptosis in human pancreatic cancer

Abstract

Objective To investigate the impact of down-regulation of histone methyltransferase enhancer of zeste homolog 2 (EZH2) on RUNX3 expressions, proliferation and apoptosis in human pancreatic cancer. Methods The expressions of EZH2 and RUNX3 in 38 pancreatic cancer patients and human pancreatic cancer AsPC-1, PANC-1 and BxPC-3 cells were detected by immunohistochemistry and western blot, respectively. Cells were transfected with siEZH2 by lipofectamin 2000. Real time-PCR and western blot were used to detect EZH2 and RUNX3 expressions. Cell growth and apoptosis in vitro and vivo were assessed by MTT, flow cytometry and nude mice experiments, respectively. The correlation among the expressions of EZH2, clinical pathological features and overall survival rate were analyzed. Results Elevated EZH2 and decreased RUNX3 expressions were observed in human pancreatic cancer tissues and cells (P<0.05). Knockdown of EZH2 reduced cell growth and induced apoptosis in vitro and vivo by upregulating RUNX3 protein expression (P<0.05). In addition, the EZH2 expressions were correlated with tumor stage, lymph node metastasis and poor prognosis (P<0.05). Conclusions EZH2 expressions were correlated with malignancy and poor prognosis in pancreatic cancer. Tumor cell proliferation was promoted by EZH2 through down-regulation of RUNX3. EZH2 may be a potential therapeutic target for pancreatic cancer. Key words: Pancreatic cancer; Gene, EZH2; Cancer suppressor gene, RUNX3; Apoptosis; Prognosis